دورية أكاديمية
أعرض في EDS

Epigenetic and pharmacological control of pigmentation via Bromodomain Protein 9 (BRD9).

التفاصيل البيبلوغرافية
العنوان: Epigenetic and pharmacological control of pigmentation via Bromodomain Protein 9 (BRD9).
المؤلفون: Basuroy T; Department of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA., Dreier M; Department of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA., Baum C; Department of Pathology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA., Blomquist T; Department of Pathology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA., Trumbly R; Department of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.; Department of Medical Education, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA., Filipp FV; Metaflux, Broadway, San Diego, California, USA.; Cancer Systems Biology, Institute for Diabetes and Cancer, Helmholtz Zentrum München, Munich, Germany.; School of Life Sciences Weihenstephan, Technical University München, Freising, Germany., de la Serna IL; Department of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
المصدر: Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2023 Jan; Vol. 36 (1), pp. 19-32. Date of Electronic Publication: 2022 Oct 03.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Blackwell Munksgaard Country of Publication: England NLM ID: 101318927 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1755-148X (Electronic) Linking ISSN: 17551471 NLM ISO Abbreviation: Pigment Cell Melanoma Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Blackwell Munksgaard,
مواضيع طبية MeSH: Melanins*/metabolism , Pigmentation Disorders*/metabolism, Infant, Newborn ; Humans ; Mice ; Animals ; Melanocytes/metabolism ; Cell Differentiation ; Epigenesis, Genetic ; Pigmentation ; DNA Helicases/metabolism ; Nuclear Proteins/metabolism ; Transcription Factors/metabolism
مستخلص: Lineage-specific differentiation programs are activated by epigenetic changes in chromatin structure. Melanin-producing melanocytes maintain a gene expression program ensuring appropriate enzymatic conversion of metabolites into the pigment, melanin, and transfer to surrounding cells. During neuroectodermal development, SMARCA4 (BRG1), the catalytic subunit of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes, is essential for lineage specification. SMARCA4 is also required for development of multipotent neural crest precursors into melanoblasts, which differentiate into pigment-producing melanocytes. In addition to the catalytic domain, SMARCA4 and several SWI/SNF subunits contain bromodomains which are amenable to pharmacological inhibition. We investigated the effects of pharmacological inhibitors of SWI/SNF bromodomains on melanocyte differentiation. Strikingly, treatment of murine melanoblasts and human neonatal epidermal melanocytes with selected bromodomain inhibitors abrogated melanin synthesis and visible pigmentation. Using functional genomics, iBRD9, a small molecule selective for the bromodomain of BRD9 was found to repress pigmentation-specific gene expression. Depletion of BRD9 confirmed a requirement for expression of pigmentation genes in the differentiation program from melanoblasts into pigmented melanocytes and in melanoma cells. Chromatin immunoprecipitation assays showed that iBRD9 disrupts the occupancy of BRD9 and the catalytic subunit SMARCA4 at melanocyte-specific loci. These data indicate that BRD9 promotes melanocyte pigmentation whereas pharmacological inhibition of BRD9 is repressive.
(© 2022 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)
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فهرسة مساهمة: Keywords: BRD9; SWI/SNF; bromodomain; chromatin remodeling; epigenetic; melanocyte differentiation; melanoma; pigmentation
المشرفين على المادة: 0 (Melanins)
EC 3.6.1.- (SMARCA4 protein, human)
EC 3.6.4.- (DNA Helicases)
0 (Nuclear Proteins)
0 (Transcription Factors)
0 (BRD9 protein, human)
تواريخ الأحداث: Date Created: 20220916 Date Completed: 20221230 Latest Revision: 20230415
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10091956
DOI: 10.1111/pcmr.13068
PMID: 36112085
قاعدة البيانات: MEDLINE
الوصف
تدمد:1755-148X
DOI:10.1111/pcmr.13068